Interictal epileptiform discharges show distinct spatiotemporal and morphological patterns across wake and sleep

Abstract

Presurgical evaluation of mesial temporal and neocortical focal pharmacoresistant epilepsy patients using intracranial EEG recordings has led to the generation of extensive data on interictal epileptiform discharges, located within or remotely from seizure onset zones. In this study, we used this data to investigate how interictal epileptiform discharges are modulated and how their spatial distribution changes during wake and sleep and analysed the relationship between these discharge events and seizure onset zones. Preoperative evaluation data from 11 adult patients with focal pharmacoresistant epilepsy were extracted from the Epilepsiae database. Interictal epileptiform discharges were automatically detected during wakefulness and over several hours of continuous seizure-free sleep (total duration of EEG recordings:106.7 h; mean per patient: 9.7 h), and analysed across four brain areas (mesial temporal, lateral neocortical, basal cortical and the temporal pole). Sleep stages were classified manually from scalp EEG. Discharge events were characterized according to their rate and morphology (amplitude, sharpness and duration). Eight patients had a seizure onset zone over mesial areas and three patients over lateral neocortical areas. Overall, discharge rates varied across brain areas during wakefulness and sleep [wake/sleep stages × brain areas interaction; Wald χ2(df = 6) = 31.1, P < 0.0001]. N2–N3 non-rapid eye movement sleep increased interictal epileptiform discharges in mesial areas compared with wakefulness and rapid eye movement sleep (P < 0.0001), and to other areas (P < 0.0001 for all comparisons). This mesial pattern was observed both within and outside of seizure onset zones. During wakefulness, the rate of interictal epileptiform discharges was significantly higher than during N2–N3 non-rapid eye movement sleep (P = 0.04), and rapid eye movement sleep (P = 0.01) in lateral neocortical areas (referred to as lateral neocortical pattern), a finding that was more pronounced in seizures onset zones (P = 0.004). The morphological characteristics of the discharge events were modulated during wakefulness and sleep stages across brain areas. The effect of seizure onset zones on discharge morphology was conditioned by brain area and was particularly marked in temporal pole areas. Our analysis of discharge patterns in relation to cerebral localization, vigilance state and the anatomical affiliation of seizure onset zones revealed the global and local aspects of the complex relationship between interictal discharges, sleep and seizure onset zones. This novel approach may lead to a better understanding of cognitive decline and responses to therapy, as well as to adaptation of surgical interventions for epileptic patients.

Rapid eye movement sleep affects interictal epileptic activity differently in mesiotemporal and neocortical areas

“…Although this regional effect was shown in NREM sleep, 13,14 previous studies did not find an effect of brain areas on IED rates in REM sleep and wakefulness. 14 Relative to wakefulness, neocortical regions showed a suppression of IEDs by REM sleep, whereas mesiotemporal regions showed an increase in IEDs. This effect was observed in both SOZ and non-SOZ regions and may be due to major cholinergic innervations to neocortical regions, mediating neuronal desynchronization, resulting in more suppression of epileptic activity in the neocortex.…”

“…Emerging evidence suggests that the spatial distribution of IEDs during sleep may extend beyond the EZ 13,14 . Specifically, mesiotemporal regions show higher IED rates during NREM sleep, regardless of whether they contain the SOZ 13 .…”

“…13 At the lobar level, the spatial modulation of IEDs varies across vigilance states, 14 with mesiotemporal regions showing peak IEDs in NREM sleep, and lateral neocortical regions displaying the highest IED rates in wakefulness. 14 While REM sleep decreases IED rates and extent, some studies have also reported the presence of IEDs in novel spatial coordinates exclusive to REM sleep. [15][16][17][18] This indicates widespread IED distribution not confined to the EZ.…”

Sleep increases firing rate modulation during interictal epileptic activities in mesial temporal structures

“…Using invasive EEG, Penfield and Jasper (1954) later reported an increase of IEDs when certain patients became drowsy or fell asleep. Since then, IEDs have been consistently found to occur more often during sleep (Lieb et al, 1980; Ferrillo et al, 2000; Bagshaw et al, 2009; Goncharova et al, 2009; Karoly et al, 2016; Rossi et al, 1984; Sammaritano et al, 1991; Spencer et al, 2016; Lambert et al, 2018; Fouad et al, 2022). Indeed, long-term recordings have found robust 24 hour periods, peaking between midnight and 5pm (Anderson et al, 2015; Spencer et al, 2016; Baud et al, 2018).…”

“…Del Felice et al (2015) reported a statistical increase in the amplitude of cortical and mesial temporal spikes during N2 versus wakefulness, but these findings were based on a very limited number of observations (an average of 39 spikes in N2, 21 spikes during wakefulness, none during SWS or REM). Recently, Fouad et al (2022) investigated differences in spike morphology using a feature extraction method (Liu et al, 2013), reporting amplitude differences between brain regions and SOZ, but no statistically significant differences between sleep stages. A non-significant trend towards increased amplitudes in deeper stages of sleep could be observed, but only within median brain regions, and only from the SOZ.…”